The chemistry of nitroso-compounds. Part 15. Formation of N-nitrosamines in solution from gaseous nitric oxide in the presence of iodine

Abstract

Quantitative results are reported for the N-nitrosation of piperidine, morpholine, and N-methylpiperazine by NO (saturated) and iodine under anaerobic conditions in solvent EtOH, EtOH–water, and MeCN at 25 °C. The reactions are very much faster than those with NO in the absence of iodine, with maximum yields of N-nitrosamine being obtained in ca. 5–30 min depending on the solvent. The rates, however, are largely independent of the initial concentrations of either amine or iodine, and are similar for all three amines despite their different basicities. With excess of amine, 2 moles of N-nitrosamine are obtained per mole of iodine. Otherwise, the limiting yields of N-nitrosamine depend on both the concentration and basicity of the amine, with ca. 50, 66, and 100% reacting for piperidine, morpholine, and N-methylpiperazine, respectively. Addition of NaOH to the reaction solution, however, increases the yield to 100% throughout. Both added NaN₃ and thiourea inhibit the formation of N-nitrosamines. The mechanism of these reactions is considered to involve rate-limiting formation of NOI (principally from NO and I₂) followed by rapid reaction with the amine base. The amine cation is unreactive; NaN₃ and thiourea inhibit reaction by competing for the NOI reagent. The results are also discussed in relation to human exposure to carcinogenic N-nitrosamines.